Project Summary The existing project (1 RF1 AG054442-01) is funded to assess the prevalence and incidence of Alzheimer?s disease (AD), and cognitive impairment in two low cardiovascular disease risk populations, the Tsimane and Moseten of lowland Bolivia. The Tsimane are a traditional horticultural population with evidence of extremely low rates of coronary atherosclerosis1. The Moseten, who are closely related genetically to the Tsimane are more market-integrated horticulturalists, due to earlier missionization and road access. Aim 1 of the existing project is to conduct a longitudinal assessment of cognitive impairment and dementia. Aim 2 is to conduct neuroimaging Aim 3 of the existing project focuses on evaluating how cerebral atrophy and cognitive impairment relate to atherosclerosis, infection history, and Apolipoprotein E (APOE) genotypes among these two populations. This Administrative Supplement proposal to Promote Diversity in Health-Related Research is designed to provide training for an exceptional postdoctoral scholar, Dr. Angela Garcia, to both enhance her skills in genetics and genomics, and augment the goals in Aim 3 of the current R01. The proposed research plan for Dr. Garcia involves training her in a 'complex systems' approach, with a specific focus on full transcriptome gene expression (RNA-sequencing, RNA-seq), in relation to genotype, immune system activation and diagnoses of morbidity and cognitive impairment. The goal of this training is to evaluate the effects of the APOE4 allele on immune function, cognitive impairment, and AD risk. Women with the APOE4 allele have significantly higher AD risk2, and this proposal will examine sex specific interactions between APOE4 and immune function to better understand why women are at such higher risk of AD. In addition, this project will explore the influences of genotype and pathogen burden on immune pathways, and their association with cognitive impairment. The sample includes PAXgene RNA samples from n=663 Tsimane and Moseten participants over 55 years old. Full transcriptome gene expression (RNA-sequencing, RNA-seq) will be extracted from those samples to analyze the expression of immune-related genes. Statistical analysis will examine the association of those expression data with APOE genotype, and parasite and pathogen burdens. We will also examine whether the association of APOE genotype with immune-related gene expression differs by sex.